The murine thrombospondin 3 gene which encodes a epithelial mucin, thrombospondin (TSP3), and the glucocerebrosidase gene, which encodes a lysososmal hydrolase, glucocerebrosidase (GC), are closely linked on the same chromosome, 3E-F1 (Bomstein, P. et al. (1995) Proc. Natl. Acad. Sci. 92:4547-51). TSP3 is a member of a family of at least three thrombospondin proteins encoded by homologous genes in both human and mouse. TSPs are glycoproteins that are secreted by a wide variety of epithelial and mesenchymal cells and are involved in developmental changes in the embryo and in response to injury in the adult. In addition, TSPs foster neurite outgrowth, stimulate and inhibit cell growth and migration, and inhibit angiogenesis (Bornstein, P. (1992) FASEB J. 6:3290-99). GC is a lysosomal hydrolase that degrades glucosylceramide, and a deficiency in this enzyme causes the most common form of lysosomal storage disease, Gaucher disease (Bornstein et al., supra).
A third gene was found in the region between the genes for TSP3 and GC which has been termed metaxin (MTX) from the greek "in between" (Bornstein et al., supra). A similar arrangement of genes is found in humans (Long, G.L. et al. (1996) Genomics 33:177-84). MTX and TSP3 share a common promoter sequence, and the initial nuclear transcripts of MTX and GC may overlap. Thus coordinate regulation of expression of these three genes may reflect metabolic interrelationships among GC, TSP3, and MTX. Metaxin is expressed ubiquitously in tissues of the young adult mouse. Although the specific function of MTX is unknown, a mutation in the mouse gene is lethal early in embryonic gestation and suggests that MTX may be required for embryonic development.
MTX is approximately 90% identical in mouse and human. It is characterized by relatively high levels (10-15%) of leucine, and acidic and basic residues. MTX is a mitochondrial protein encoded by a nuclear gene, but does not contain an amino-terminal signal sequence or N-glycosylation sites. A putative hydrophobic transmembrane domain is found near the carboxy-terminus.
The discovery of a new metaxin protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of cancer, immune disorders, and developmental disorders.